[Testosterone impairs insulin sensitivity in 3T3-L1 adipocytes and the related nongenomic mechanisms].
OBJECTIVE
To investigate the influence of rapid nongenomic effect of androgen on the insulin sensitivity of mature adipocytes and the molecular mechanism thereof.


METHODS
Fetal mice [corrected] preadipocytes of the line 3T3-L1 were cultured to develop into mature adipocytes. 3T3-L1 adipocytes were pretreated with testosterone of the concentration of 10-9 to approximately 10(-5) mol/L for a short-time 0-30 minutes) or a long-time (24 hours). Insulin (Ins) 200 microl at the concentration 100 micromol/L and 2-deoxy [3H] glucose were added to examine the glucose uptake. Phosphorylation and protein expression of Ins receptor (InsR) and its downstream signaling molecules (Akt and GSK3beta) were analyzed by Western blotting.


RESULTS
The Ins-stimulated glucose uptake after the pretreatment of testosterone for 30 min and 24 h decreased gradually in response to the increasing of the concentration of testosterone with the nadir both at the testosterone concentration of 10(-5) mol/L (both P < 0.05). The phosphorylation levels of InsR, Akt, and GSK3Pbeta were significantly down-regulated by adding of testosterone at the concentration of 10(-6) mol/L for 3-30 minutes (all P < 0.05) or by adding of testosterone at the concentrations of 10(-7) - 10(-6) mol/L for 24 hours (all P < 0.05). The protein expression levels of InsR, Akt, and GSK3Pbeta, however, were not significantly affected by testosterone treatment.


CONCLUSIONS
Rapid nongenomic effect of androgen may contribute to the insulin resistance in adipocytes.
Chen
Min
M
Department of Obstetrics, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
Xu
Wen
W
Su
Chun-lin
CL
Lin
Jin-fang
JF
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000493:pharmacokinetics; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology*
D007328:Insulin; D013739:Testosterone; D011972:Receptor, Insulin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose